Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERß.

Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERß), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERß. We used immunohistochemical assays to verify that AURKA and ERß were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERß. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERß-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERß. AURKA may represent a new target for the treatment of ovarian EMs.

Salidroside alleviates LPS-induced liver injury and inflammation through SIRT1- NF-κB pathway and NLRP3 inflammasome.

Objectives: Salidroside (SAL), an active ingredient purified from the medicinal plant Rhodiola rosea, has anti-inflammatory, anti-oxidant, anticancer, and neuroprotective properties. The study aims to examine SAL's protective role in liver damage brought on by lipopolysaccharide (LPS). Materials and Methods: Six to eight-week-old male C57BL/6 wild-type mice were intraperitoneally treated with 10 mg/kg LPS for 24 hr and 50 mg/kg SAL two hours before LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT1, NF-кB, NLRP3, cleaved caspase-1, and GSDMD, respectively. Results: Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-1ß, TNF-α, and IL-6 pro-inflammatory cytokines after being induced by LPS (all, P<0.001). The western blotting examination results demonstrated that SAL increased the levels of Sirtuin 1 (SIRT1) expression but markedly reduced the phosphorylation of Nuclear Factor Kappa B (NF-B) and the expressions of NLRP3, cleaved caspase-1, and gasdermin D (GSDMD) induced by LPS (all, P<0.001). Conclusion: Our results speculated that by inhibiting the SIRT1- NF-κB pathway and NLRP3 inflammasome, SAL defends against LPS-induced liver injury and inflammation.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation.

BACKGROUND: Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. METHODS: The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 µg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. RESULTS: XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. CONCLUSION: XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Male, female, and mixed-sex poplar plantations support divergent soil microbial communities.

Males and females of dioecious plants have sex-specific adaptations to diverse habitats. The effects of inter- and intrasexual interactions in poplar plantations on composition, structure, and function of soil microbiota have not been explored in degraded areas. We conducted a series of greenhouse and field experiments to investigate how belowground competition, soil microbial communities, and seasonal variation nitrogen content differ among female, male, and mixed-sex Populus cathayana plantations. In the greenhouse experiment, female neighbors suppressed the growth of males under optimal nitrogen conditions. However, male neighbors enhanced stable isotope ratio of nitrogen (δ15 N) of females under intersexual competition. In the field, the root length density, root area density, and biomass of fine roots were lower in female plantations than in male or mixed-sex plantations. Bacterial networks of female, male, and mixed-sex plantations were characterized by different composition of hub nodes, including connectors, modules, and network hubs. The sex composition of plantations altered bacterial and fungal community structures according to Bray-Curtis distances, with 44% and 65% of variance explained by the root biomass, respectively. The total soil nitrogen content of mixed-sex plantation was higher than that in female plantation in spring and summer. The mixed-sex plantation also had a higher ß-1,4-N-acetyl-glucosaminidase activity in summer and a higher nitrification rate in autumn than the other two plantations. The seasonal soil N content, nitrification rate, and root distribution traits demonstrated spatiotemporal niche separation in the mixed-sex plantation. We argue that a strong female-female competition and limited nitrogen content could strongly impede plant growth and reduce the resistance of monosex plantations to climate change and the mixed-sex plantations constitutes a promising way to restore degraded land.

Multidimensional detection enabled by twisted black arsenic-phosphorus homojunctions.

A light field carrying multidimensional optical information, including but not limited to polarization, intensity and wavelength, is essential for numerous applications such as environmental monitoring, thermal imaging, medical diagnosis and free-space communications. Simultaneous acquisition of this multidimensional information could provide comprehensive insights for understanding complex environments but remains a challenge. Here we demonstrate a multidimensional optical information detection device based on zero-bias double twisted black arsenic-phosphorus homojunctions, where the photoresponse is dominated by the photothermoelectric effect. By using a bipolar and phase-offset polarization photoresponse, the device operated in the mid-infrared range can simultaneously detect both the polarization angle and incident intensity information through direct measurement of the photocurrents in the double twisted black arsenic-phosphorus homojunctions. The device's responsivity makes it possible to retrieve wavelength information, typically perceived as difficult to obtain. Moreover, the device exhibits an electrically tunable polarization photoresponse, enabling precise distinction of polarization angles under low-intensity light exposure. These demonstrations offer a promising approach for simultaneous detection of multidimensional optical information, indicating potential for diverse photonic applications.

Enterotoxigenic Bacteroides fragilis (ETBF) Enhances Colorectal Cancer Cell Proliferation and Metastasis Through HDAC3/miR-139-3p Pathway.

Enterotoxigenic Bacteroides fragilis (ETBF) is believed to promote the malignant process of colorectal cancer (CRC), but the underlying molecular mechanism still needs to be revealed. CRC cells (SW480 and HCT-116) were treated with ETBF strain. Cell proliferation, invasion and, migration were evaluated by cell counting kit 8 assay, EdU assay, colony formation assay, transwell assay, and wound healing assay. Protein expression was analyzed by western blot. MicroRNA (miR)-139-3p and histone deacetylase 3 (HDAC3) expression levels in tissues and cells were determined by qRT-PCR. Xenograft tumor model was conducted to evaluate the effect of miR-139-3p on CRC tumor growth. ETBF treatment could promote CRC cell proliferation, invasion and migration. MiR-139-3p expression was decreased by ETBF, and its overexpression reversed the effect of ETBF on CRC cell progression. HDAC3 negatively regulated miR-139-3p expression, and its overexpression facilitated CRC cell behaviors via reducing miR-139-3p expression. Moreover, HDAC3 expression was increased by ETBF, and its knockdown also abolished ETBF-mediated CRC cell progression. Additionally, miR-139-3p overexpression could reduce CRC tumor growth in vivo. ETBF aggravated CRC proliferation and metastasis via the regulation of HDAC3/miR-139-3p axis. The discovery of ETBF/HDAC3/miR-139-3p axis may provide a new direction for CRC treatment.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Long wavelength mid-infrared multi-gases spectroscopy using tunable single-mode slot waveguide quantum cascade laser.

Single-mode tunable quantum cascade lasers (QCLs) are promising for high-resolution and highly sensitive trace gases sensing across the mid-infrared (MIR) region. We report on the development of a tunable single-mode slot waveguide QCL array in the long wavelength part of the MIR regime (>12 µm). This laser array exhibits a tuning range of around 12 cm-1, from 735.3 to 747.3 cm-1. Using this developed single-mode tunable QCL, we demonstrate individual gas sensing, yielding the detection limit of 940 ppb and 470 ppb for acetylene and o-xylene, respectively. To verify the potential of the developed QCL array in multi-species gas detection, laser absorption measurements of two mixed gases of acetylene and o-xylene were conducted, showing the absorption features of the corresponding gases agree well with the theoretical predictions.

Allicin protects against LPS-induced cardiomyocyte injury by activating Nrf2-HO-1 and inhibiting NLRP3 pathways.

BACKGROUND: Allicin is a bioactive compound with potent antioxidative activity and plays a protective effect in myocardial damage and fibrosis. The role and mechanism of Allicin in septic cardiomyopathy are unclear. In this study, we investigated the effects and underlying mechanisms of Allicin on lipopolysaccharide (LPS) induced injury in H9c2 cardiomyocytes. METHODS: H9c2 cardiomyocyte cells were pretreated with Allicin (0, 25, 50, and 100 µM) for 2 h, followed by incubation with LPS (10 µg/mL) for 24 h at 37 °C. Cell viability (cell counting kit-8 [CCK-8]), apoptosis (TUNEL staining), oxidative stress (malondialdehyde [MDA] and superoxide dismutase [SOD]), and cytokines release (Interleukin beta [IL-ß], Interleukin 6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) were determined. The mRNA and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NLR family pyrin domain containing 3 (NLRP3) signaling pathway molecules were quantified by real-time quantitative PCR (RT-qPCR) and western blot, respectively. RESULTS: Allicin had no effect on H9c2 cell viability but attenuated LPS-induced injury, with increased cell viability, reduction in inflammatory cytokines release, apoptosis, reduced MDA, and increased SOD (P < 0.05). Additionally, Allicin increased Nrf2 and cellular HO-1 expressions in LPS-treated H9c2 cells. Moreover, Allicin modulated the NLRP3 inflammasome, increased the cleaved caspase-1 (p10) protein, and attenuated the LPS-induced increase in NLRP3, pro-IL-1ß, and IL-1ß proteins. Silencing of Nrf2 by siRNA (siNrf2) significantly attenuated Allicin-induced increase in cell viability and HO-1 and decrease in NLRP3 protein in LPS-stimulated H9c2 cells. CONCLUSIONS: Allicin protects cardiomyocytes against LPS­induced injury through activation of Nrf2/HO-1 and inhibition of NLRP3 signaling pathways.

Quantifying Interfacial Bonding Using Thermal Boundary Conductance at Cubic Boron Nitride/Copper Interfaces with a Large Mismatch of Phonon Density of States.

Interfacial bonding that directly influences the functional and mechanical properties of metal/nonmetal composites is commonly estimated by destructive pull-off measurements such as scratch tests, etc. However, these destructive methods may not be applicable under certain extreme environments; it is urgently necessary to develop a nondestructive quantification technique to determine the composite's performance. In this work, the time-domain thermoreflectance (TDTR) technique is applied to study the inter-relationship between interfacial bonding and interface characteristics through thermal boundary conductance (G) measurements. We think that interfacial phonon transmission capability plays a decisive role in influencing interfacial heat transport, especially for scenarios with a large mismatch of phonon density of states (PDOS). Moreover, we demonstrated this method at (100) and (111) cubic boron nitride/copper (c-BN/Cu) interfaces by both experimental and simulation efforts. The results show that the TDTR-measured G of the (100) c-BN/Cu interface (30 MW/m2·K) is about 20% higher than that of the (111) c-BN/Cu (25 MW/m2·K), which is ascribed to that higher interfacial bonding of the (100) c-BN/Cu endows it with better interfacial phonon transmission capability. In addition, detailed comparison of 10+ other metal/nonmetal interfaces exhibits similar positive relationship for interfaces with a large PDOS mismatch but negative relationship for interfaces with a small PDOS mismatch. The latter one is attributed to that extra inelastic phonon scattering and electron transport channels abnormally promoting interfacial heat transport. This work may provide some insights into quantitatively establishing inter-relationship between interfacial bonding and interface characteristics.

Long-wave infrared photothermoelectric detectors with ultrahigh polarization sensitivity.

Filter-free miniaturized polarization-sensitive photodetectors have important applications in the next-generation on-chip polarimeters. However, their polarization sensitivity is thus far limited by the intrinsic low diattenuation and inefficient photon-to-electron conversion. Here, we implement experimentally a miniaturized detector based on one-dimensional tellurium nanoribbon, which can significantly improve the photothermoelectric responses by translating the polarization-sensitive absorption into a large temperature gradient together with the finite-size effect of a perfect plasmonic absorber. Our devices exhibit a zero-bias responsivity of 410 V/W and an ultrahigh polarization ratio (2.5 × 104), as well as a peak polarization angle sensitivity of 7.10 V/W•degree, which is one order of magnitude higher than those reported in the literature. Full linear polarimetry detection is also achieved with the proposed device in a simple geometrical configuration. Polarization-coded communication and optical strain measurement are demonstrated showing the great potential of the proposed devices. Our work presents a feasible solution for miniaturized room-temperature infrared photodetectors with ultrahigh polarization sensitivity.

Pseudotargeted metabolomics-based random forest model for tracking plant species from herbal products.

BACKGROUND: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions. PURPOSE: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products. METHODS: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products. RESULTS: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products. CONCLUSION: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.

Extreme Polarization Anisotropy in Resonant Third-Harmonic Generation from Aligned Carbon Nanotube Films.

Carbon nanotubes (CNTs) possess extremely anisotropic electronic, thermal, and optical properties owing to their 1D character. While their linear optical properties have been extensively studied, nonlinear optical processes, such as harmonic generation for frequency conversion, remain largely unexplored in CNTs, particularly in macroscopic CNT assemblies. In this work, macroscopic films of aligned and type-separated (semiconducting and metallic) CNTs are synthesized and polarization-dependent third-harmonic generation (THG) from the films with fundamental wavelengths ranging from 1.5 to 2.5 µm is studied. Both films exhibited strongly wavelength-dependent, intense THG signals, enhanced through exciton resonances, and third-order nonlinear optical susceptibilities of 2.50 × 10-19  m2  V-2 (semiconducting CNTs) and 1.23 × 10-19  m2  V-2 (metallic CNTs), respectively are found, for 1.8 µm excitation. Further, through systematic polarization-dependent THG measurements, the values of all elements of the susceptibility tensor are determined, verifying the macroscopically 1D nature of the films. Finally, polarized THG imaging is performed to demonstrate the nonlinear anisotropy in the large-size CNT film with good alignment. These findings promise applications of aligned CNT films in mid-infrared frequency conversion, nonlinear optical switching, polarized pulsed lasers, polarized long-wave detection, and high-performance anisotropic nonlinear photonic devices.

Electrically-pumped compact topological bulk lasers driven by band-inverted bound states in the continuum.

One of the most exciting breakthroughs in physics is the concept of topology that was recently introduced to photonics, achieving robust functionalities, as manifested in the recently demonstrated topological lasers. However, so far almost all attention was focused on lasing from topological edge states. Bulk bands that reflect the topological bulk-edge correspondence have been largely missed. Here, we demonstrate an electrically pumped topological bulk quantum cascade laser (QCL) operating in the terahertz (THz) frequency range. In addition to the band-inversion induced in-plane reflection due to topological nontrivial cavity surrounded by a trivial domain, we further illustrate the band edges of such topological bulk lasers are recognized as the bound states in the continuum (BICs) due to their nonradiative characteristics and robust topological polarization charges in the momentum space. Therefore, the lasing modes show both in-plane and out-of-plane tight confinements in a compact laser cavity (lateral size ~3λlaser). Experimentally, we realize a miniaturized THz QCL that shows single-mode lasing with a side-mode suppression ratio (SMSR) around 20 dB. We also observe a cylindrical vector beam for the far-field emission, which is evidence for topological bulk BIC lasers. Our demonstration on miniaturization of single-mode beam-engineered THz lasers is promising for many applications including imaging, sensing, and communications.

Epstein-Barr virus-induced infection-associated hemophagocytic lymphohistiocytosis with acute liver injury: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory reaction, which is rare and life-threatening. According to the pathogen, HLH is divided into genetic and acquired. The most common form of acquired HLH is infection-associated HLH, of which Herpes viruses, particularly Epstein-Barr virus (EBV), are the leading infectious triggers. However, it is difficult to distinguish between simple infection with EBV and EBV-induced infection-associated HLH since both can destroy the whole-body system, particularly the liver, thereby increasing the difficulty of diagnosis and treatment. CASE SUMMARY: This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury, aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH. The patient was categorized as acquired hemophagocytic syndrome in adults. After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response, gamma globulin enhanced immunotherapy, the patient recovered. CONCLUSION: From the diagnosis and treatment of this patient, attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients' survival.

PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis.

Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis.

Astragaloside IV attenuates lipopolysaccharide induced liver injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation.

Aims and objectives: Sepsis-associated liver injury is a common public health problem in intensive care units. Astragaloside IV (AS-IV) is an active component extracted from the Chinese herb Astragalus membranaceus, and has been shown to have anti-oxidation, anti-inflammation, and anti-apoptosis properties. The research aimed to investigate the protective effect of AS-IV in lipopolysaccharide (LPS)-induced liver injury. Methods: Male C57BL/6 wild-type mice (6-8 week-old) were intraperitoneally injected with 10 mg/kg LPS for 24 h and AS-IV (80 mg/kg) 2 h before the LPS injection. Biochemical and histopathological analyses were carried out to assess liver injury. The RT-qPCR analyzed the mRNA expression of IL-1ß, TNF-α, and IL-6. The mRNA and protein expression of SIRT1, nuclear Nrf2, Nrf2, and HO-1 were measured by Western blotting. Results: Serum alanine/aspartate aminotransferases (ALT/AST) analysis, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were showed that AS-IV protected against LPS-induced hepatotoxicity. The protection afforded by AS-IV was confirmed by pathological examination of the liver. Pro-inflammatory cytokines, including interleukin- 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were observed to be reversed by AS-IV after exposure to LPS. Western blot analysis demonstrated that AS-IV enhanced the expression levels of Sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). Conclusions: AS-IV protects against LPS-induced Liver Injury and Inflammation by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation.